Vitamin C as a Cardioprotective Agent Against Doxorubicin-Induced Cardiotoxicity

Abstract

Doxorubicin is used and highly effective chemotherapeutic agent; however, its clinical utility remains limited by dose-dependent cardiotoxicity, presenting a significant challenge in cancer management. Growing preclinical research and clinical evidence suggest that the antioxidant vitamin C (ascorbic acid) may confer cardioprotective effects against doxorubicin-induced cardiotoxicity. In this review, both preclinical and clinical research has been synthesized to assess the potential role of vitamin C in mitigating doxorubicin-induced cardiotoxicity. Preclinical data have routinely indicated that vitamin C can reduce oxidative stress, preserve mitochondrial function, and modulate proinflammatory cytokine levels. Additionally, animal models have demonstrated promising results in maintaining cardiomyocyte structural integrity. In this capacity, vitamin C may be an effective adjunctive therapeutic for attenuating cardiac injury. Conversely, the clinical data remain variable, with emerging evidence supporting the notion that vitamin C can serve as a safe adjunct that preserves cardiac function during anthracycline therapy. Further investigation is warranted to optimize dosing, timing, and delivery routes and better elucidate the exact molecular mechanisms of these protective effects. This review emphasizes key molecular mechanisms, such as oxidative and nitrosative stress, mitochondrial dysfunction, and inflammatory signaling, in the myocardium, and examines the role of vitamin C supplementation, alone or in combination with doxorubicin, on myocardial damage markers and cardiomyocyte viability.

Keywords: cardioprotection; doxorubicin‐induced cardiotoxicity; oxidative stress; reactive oxygen species; vitamin C.

Figure 1. Schematic demonstration of the protective role of vitamin C against doxorubicin‐induced cardiotoxicity.

DR indicates death receptor; ROS, reactive oxygen species; and TNFR1, tumor necrosis factor receptor 1.

Figure 2. Schematic demonstration of the cardioprotective mechanisms vitamin C.

ARE indicates antioxidant response element; eNOS, endothelial nitric oxide synthase; GPx, glutathione peroxidase; HO‐1, heme oxygenase‐1; IKK, IkB kinase; IL, interleukin; JNK, c‐Jun N‐terminal kinase; KEAP1, Kelch‐like ECH‐associated protein 1; NF‐κB, nuclear factor kappa B; NQO1, NAD(P)H:quinone oxidoreductase; Nrf2, nuclear factor erythroid 2‐related factor 2; ROS, reactive oxygen species; and TNF‐ α, tumor necrosis factor alpha.